4-Methylmorpholine → HCID 86619965, compound

Participants

Reaction Steps

A solution of crude (S)-2-(tert-butoxycarbonyl)-3-(cyclopropyl(pent-4-enyl)amino)propanoic acid 1b (1.47 g, 4.71 mmoL) in 20 mL of DCM was treated sequentially with (1R,2 S)-ethyl 1-((3R,5S)-3-hydroxypyrrolidine-5-carboxamido)-2-vinylcyclopropanecarboxylate hydrochloride (1.44 g, 4.71 mmoL), N-methyl morpholine (1.80 mL, 16.3 mmoL), and HATU (2.14 g, 5.53 mmoL). The reaction mixture was stirred at rt under N2 for 3 h, and then concentrated in vacuo. The residue was dissolved in water, and 1N HCl was added until the pH=5. This aqueous solution was extracted with EtOAc (3×). The combined organic phases were washed with sat. aq. NaHCO3, dried (MgSO4), and concentrated in vacuo to give the crude product. Flash chromatography (50% ethyl acetate/hexane to 100% ethyl acetate) gave 1.55 g (58%) of (1R,2S)-ethyl 1-((3R,5S)-1-((S)-2-(tert-butoxycarbonyl)-3-(cyclopropyl(pent-4-enyl)amino)propanoyl)-3-hydroxypyrrolidine-5-carboxamido)-2-vinylcyclopropanecarboxylate 1c as a white foam: LC-MS (Phenomenex-Luna S10 HPLC column: 3.0×50 mm length. Gradient: 100% Solvent A/0% Solvent B to 0% Solvent A/100% Solvent B. Gradient time: 2 min. Hold time: 1 min. Flow rate: 4 mL/min. Detector Wavelength: 220 nm. Solvent A: 10% MeOH/90% H2O/0.1% TFA. Solvent B: 10% H2O/90% MeOH/0.1% TFA.) (Retention time: 1.38 min), MS m/z 564 (M++1).

Provenance & Evidence